Improving the survival of grafted dopaminergic neurons: a review over current approaches.

摘要: Neural transplantation is developing into a therapeutic alternative in Parkinson's disease. A major limiting factor that only 3-20% of grafted dopamine neurons survive the procedure. Recent advances regarding how and when die indicate events preceding actual tissue implantation during first week thereafter are crucial, apoptosis plays pivotal role. Triggers may initiate neuronal death grafts include donor hypoxia hypoglycemia, mechanical trauma, free radicals, growth deprivation, excessive extracellular concentrations excitatory amino acids host brain. Four distinct phases grafting can involve cell have been identified: retrieval embryo; dissection preparation tissue; procedure followed by immediate period after graft injection; later stages maturation. During these phases, processes involving radicals caspase activation (leading to apoptosis) be triggered, possibly an increase intracellular calcium. We review different approaches reduce survival neurons, typically 2-4. For example, changes such as improved media technique beneficial. Calcium channel antagonists nimodipine flunarizine improve nigral survival. Agents counteract oxidative stress its consequences, superoxide dismutase overexpression, lazaroids significantly transplanted neurons. Also, inhibition inhibitor has marked positive effects. Finally, basic fibroblast members transforming factor-beta superfamily, glial line-derived neurotrophic factor, outcome transplants. These recent provide hope for patients with disease, reducing need human embryonic increasing likelihood successful outcome.